title: Empirical voriconazole therapy for febrile neutropenic patients with hematological disorders: a prospective multicenter trial in Japan.
abstract: An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-β-D-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31% achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7% of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-β-D-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-β-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan, hide_koh@med.osaka-cu.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Koh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Masaki
authors.initials: M
authors.lastname: Iino
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Urase
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Jun
authors.initials: J
authors.lastname: Yamanouchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Akio
authors.initials: A
authors.lastname: Urabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kanamaru
authors.forename: Tohru
authors.initials: T
authors.lastname: Masaoka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000946:Antigens, Fungal; D064147:Febrile Neutropenia / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000097:blood* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D009181:Mycoses / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D008351:Mannans; D011743:Pyrimidines; D014230:Triazoles; C012990:galactomannan; D065819:Voriconazole; D005690:Galactose